Phase I-II Trial of Intensification of the MAID Regimen With Support of Lenograstim (rHuG-CSF) in Patients With Advanced Soft-Tissue Sarcoma (STS)

This study was conducted to determine the maximum tolerated dose of an intensified MAID (mesna, adriamycin, ifosfamide, dacarbazine) regimen with the support of lenograstim in patients with advanced soft tissue sarcomas. Following 1 cycle of MAID at the standard dose, four patients were to be treated at each of five dosage levels: +25%, +45%, +65%, +85%, +100%. Sixteen patients were treated. Because there were no significant differences in hematologic toxicity between patients receiving lenograstim 5 or 10 μg/kg/day (levels 1-5 and 1-10), the data were pooled for comparison with level 2. The median duration of absolute neutrophil count < 0.5 × 109/l was 3 days at level 1 and 7 days at level 2 (p < 0.01). The median platelet nadir was 25 × 109/l at level 1 and 10 × 109/l at level 2 (p < 0.01). The median duration of toxicity-related hospitalization was 3.5 days and 11 days at levels 1 and 2, respectively, (p < 0.001). Mucositis ≥grade III occurred after 3/29 cycles at level 1 and 10/15 cycles at level 2 (p < 0.001). After 4 cycles at level 1, 8/8 patients still had performance status scores ≤2, and only 4/8 had performance status scores ≤2 after the second cycle at level 2. Lenograstim enabled an increase of 25% of the MAID regimen. At higher dose levels, severe mucositis and deterioration in performance status were dose limiting.